PF-03758309 HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H30N8OS.ClH
Molecular Weight	527.085
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN(C)C[C@@H](NC(=O)N1CC2=C(NC3=C4SC=CC4=NC(C)=N3)NN=C2C1(C)C)C5=CC=CC=C5

InChI

InChIKey=DZSGSCZKFHGJNK-FSRHSHDFSA-N

InChI=1S/C25H30N8OS.ClH/c1-15-26-18-11-12-35-20(18)23(27-15)29-22-17-13-33(25(2,3)21(17)30-31-22)24(34)28-19(14-32(4)5)16-9-7-6-8-10-16;/h6-12,19H,13-14H2,1-5H3,(H,28,34)(H2,26,27,29,30,31);1H/t19-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C25H30N8OS
Molecular Weight	490.624
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24366569
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20439741 | https://www.ncbi.nlm.nih.gov/pubmed/23543898 | https://www.ncbi.nlm.nih.gov/pubmed/24432870

PF-3758309 was developed as an ATP-competitive inhibitor of PAK4. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50 = 1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50 = 4.7 nM). PF-3758309 blocks the growth of multiple human tumor xenografts, with a plasma EC50 value of 0.4 nM in the most sensitive model. PF-3758309 is antiproliferative and induces apoptosis in an HCT116 tumor model.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase PAK 4 3 Target ID: CHEMBL4482 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432870	Inhibitor 8504		36.0 nM [Ki]
Serine/threonine-protein kinase PAK 1 5 Target ID: CHEMBL4600 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24432870	Inhibitor 8504		36.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Colon cancer 66 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23543898	Primary		Basic research	Unknown Approved Use Unknown
Lung cancer 70 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24366569	Primary		Basic research	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677350	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23524533/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23524533/	yes

PubMed

Title	Date	PubMed
p21-activated kinase 1 activity is required for histone H3 Ser10 phosphorylation and chromatin condensation in mouse oocyte meiosis.	2017-07	27166635
Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells.	2016-09-20	27542207

Patents

Sample Use Guides

In Vivo Use Guide

Five- to six-week-old female athymic nude mice bearing colorectal cancer xenograft were treated for 14 days with either vehicle control (0.5% methylcellulose), or PF-3758309 (25 mg/kg) twice daily by oral gavage.

Route of Administration: Oral

In Vitro Use Guide

To evaluate the sensitivity of colorectal cancer (CRC) cell lines to PF-3758309, a panel of 27 CRC cell lines were exposed to increasing concentrations and assessed for proliferation using the SRB assay. Treatment of RKO, COLO205, HTC116, SW620, SW480, SW48, LS123, SW403, LOVO, LS180, SKC01, COLO201, LS513 and LS174T cell lines with PF-3758309 (0.1nM-1mkM) for 72 h leads to inhibition of cell proliferation (IC50< 0.0125mkM).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:53:34 GMT 2025` Edited by `admin` on `Mon Mar 31 22:53:34 GMT 2025`
Record UNII	BS52H27235
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PF-03758309 HYDROCHLORIDE SALT

Preferred Name

English

PF-03758309 HYDROCHLORIDE

Common Name

English

PYRROLO(3,4-C)PYRAZOLE-5(4H)-CARBOXAMIDE, N-((1S)-2-(DIMETHYLAMINO)-1-PHENYLETHYL)-2,6-DIHYDRO-6,6-DIMETHYL-3-((2-METHYLTHIENO(3,2-D)PYRIMIDIN-4-YL)AMINO)-, HYDROCHLORIDE (1:1)

Systematic Name

English

Code System Code Type Description

CAS

1279034-84-2

Created by admin on Mon Mar 31 22:53:34 GMT 2025 , Edited by admin on Mon Mar 31 22:53:34 GMT 2025

PRIMARY

FDA UNII

BS52H27235

Created by admin on Mon Mar 31 22:53:34 GMT 2025 , Edited by admin on Mon Mar 31 22:53:34 GMT 2025

PRIMARY

DRUG BANK

DBSALT002070

Created by admin on Mon Mar 31 22:53:34 GMT 2025 , Edited by admin on Mon Mar 31 22:53:34 GMT 2025

PRIMARY

PUBCHEM

76972060

Created by admin on Mon Mar 31 22:53:34 GMT 2025 , Edited by admin on Mon Mar 31 22:53:34 GMT 2025

PRIMARY

Related Record Type Details


					PK459EA5I2

PF-03758309

PARENT -> SALT/SOLVATE

Amount:

Related Record Type Details


					PK459EA5I2

PF-03758309

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24366569Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20439741 | https://www.ncbi.nlm.nih.gov/pubmed/23543898 | https://www.ncbi.nlm.nih.gov/pubmed/24432870

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24366569
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20439741 | https://www.ncbi.nlm.nih.gov/pubmed/23543898 | https://www.ncbi.nlm.nih.gov/pubmed/24432870

Drug as perpetrator